The present invention relates to a new process suitable for large-scale preparation of a substituted imidazopyridine compound of formula (1), wherein R1 is a C1-C6 alkoxy or NH2 group, comprising the step of reacting a compound of the formula (2) wherein R1 is a C1-C6 alkoxy or NH2 group, with a 3-halo-2-butanone compound in cyclohexanone.
A similar reaction is described in EP 33094, EP 204 285, EP 228 006, EP 308 917, and WO 99/55706 wherein a substituted aminopyridine compound of the general formula (X) is reacted with a compound of formula wherein    X is i.a. H, CH3 or an ester group, such as COOCH3 or COOC2H5,    Y is i.a. CH3, CH2CH3, and    Z is a leaving group, such as halogen, mesyl or tosyl, to give a compound of the general structure wherein X and Y are as described above.
The reaction is carried out in an inert solvent, such as acetone, alcohols, benzene, N,N-dimethylformamide, tetrahydrofurane, chloroform, or diethyl ether, preferably at elevated temperature, and optionally in the presence of an inorganic or organic base.
The reaction is characterized by long reaction times, e.g. 16 to 84 hours, high reaction temperatures and relatively low yields, e.g. 22% to 55%. The reaction is thereby not suitable for large-scale preparation of substituted imidazopyridine compounds.
We have surprisingly found that if the process of the present invention is carried out as described herein the reaction time can be shortened, the reaction temperature can be lowered and the yield is increased.